反应详情

3-Bromo-4-chloro-benzoyl chloride (Step 2A, 106.9 mmol) in acetonitrile (300 mL) was added dropwise over 30 minutes to a vigorously stirring solution of 2-methylamino-phenol (15.1 g, 122.9 mmol) and NaHCO3 (18.0 g, 213.7 mmol) in acetonitrile (200 mL) and water (200 mL). The mixture was stirred for additional 1 h and then concentrated to remove acetonitrile. The solid was filtered, washed with HCl (1N, 600 mL) and water (500 mL), and dried. The solid was dissolved in dichloromethane (500 mL) and n-butylamine (20 mL) was added. The mixture was stirred at rt for 16 hrs and concentrated. The residue was partially purified via silica gel flash chromatography (eluting with 20% to 35% ethyl acetate in hexane) and then crystallized from hexane/ethyl acetate (75/25) to give 3-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamide (20.5 g) as a white solid. MS [M+H]+: 339.7/341.8; tR=2.19 min. (method 1)

1. concentrationconcentrated
2. customto remove acetonitrile
3. filtrationThe solid was filtered
4. washwashed with HCl (1N, 600 mL) and water (500 mL)
5. customdried
6. dissolutionThe solid was dissolved in dichloromethane (500 mL)
7. additionn-butylamine (20 mL) was added
8. stirringThe mixture was stirred at rt for 16 hrs
9. concentrationconcentrated
10. customThe residue was partially purified via silica gel flash chromatography (eluting with 20% to 35% ethyl acetate in hexane)
11. customcrystallized from hexane/ethyl acetate (75/25)